Молекулярная биология, 2022, T. 56, № 5, стр. 697-709

Повышение бактерицидного эффекта антибиотиков путем ингибирования ферментов, вовлеченных в генерацию сероводорода у бактерий

Т. А. Серегина a*, К. В. Лобанов a, Р. С. Шакулов a, А. С. Миронов a

a Институт молекулярной биологии им. В.А. Энгельгардта Российской академии наук
119991 Москва, Россия

* E-mail: tatyana.s82@gmail.com

Поступила в редакцию 02.03.2022
После доработки 28.03.2022
Принята к публикации 28.03.2022

Аннотация

Борьба с возникновением и распространением бактериальных патогенов с множественной лекарственной устойчивостью, провоцирующих развитие внутрибольничных инфекций, остается актуальной задачей здравоохранения во всем мире. В обзоре рассмотрены результаты недавних исследований, показывающих, что наряду с инактивацией специфических биохимических мишеней, многие антибиотики провоцируют в бактериальных клетках развитие окислительного стресса, который повреждает клеточные макромолекулы и повышает чувствительность бактерий к антибиотикам. Ранее мы установили, что генерация сероводорода (универсального протектора бактерий от окислительного стресса) различными бактериальными патогенами защищает их от бактерицидных антибиотиков. В дальнейшем была выявлена взаимосвязь между генерацией H2S, метаболизмом цистеина и окислительным стрессом. Наконец, в наших последних работах показано, что малые молекулы, ингибирующие ферменты, вовлеченные в генерацию сероводорода, существенно повышают бактерицидный эффект антибиотиков различного типа, включая хинолоны, бета-лактамы и аминогликозиды in vitro, а также влияют на развитие инфекций в мышиных моделях. Кроме того, отобранные ингибиторы супрессируют толерантность бактерий к антибиотикам, нарушают образование биопленок и существенно снижают количество персистеров, переживающих обработку антибиотиками. Мы предполагаем, что агенты, ограничивающие биосинтез сероводорода, могут быть эффективным инструментом в борьбе с распространением бактериальных патогенов с множественной лекарственной устойчивостью.

Ключевые слова: бактерии, антибиотики, окислительный стресс, продукция сероводорода, ингибиторы ферментов биосинтеза сероводорода, антимикробные препараты

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